Pharmacological researchJul 22, 2023

HPV E7 protein helps cervical cancer grow by changing RNA modification of PAK5

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 4, 2026

Abstract

ALKBH5 was significantly upregulated in cervical cancer (CC) and may serve as a valuable prognostic marker.

HPV E6/7 oncoproteins affected global m6A modification and specifically increased ALKBH5 expression.
Forced expression of ALKBH5 enhanced malignant traits in cervical cancer cells.
E7 promoted ALKBH5 expression through mechanisms involving specific histone modifications and post-translational changes.
ALKBH5-mediated m6A demethylation increased the expression of PAK5.
The m6A reader YTHDF2 bound to PAK5 mRNA, regulating its stability based on m6A presence.
ALKBH5 contributed to tumorigenesis and metastasis in cervical cancer by regulating PAK5.

Simplified

Human papillomavirus (HPV) infection is a causative agent of cervical cancer (CC). N6-methyladenosine (m6A) modification is implicated in carcinogenesis and tumor progression. However, the involvement of m6A modification in HPV-involved CC remains unclear. Here we showed that HPV E6/7 oncoproteins affected the global m6A modification and E7 specifically promoted the expression of ALKBH5. We found that ALKBH5 was significantly upregulated in CC and might serve as a valuable prognostic marker. Forced expression of ALKBH5 enhanced the malignant phenotypes of CC cells. Mechanistically, we discovered that E7 increased ALKBH5 expression through E2F1-mediated activation of the H3K27Ac and H3K4Me3 histone modifications, as well as post-translational modification mediated by DDX3. ALKBH5-mediated m6A demethylation enhanced the expression of PAK5. The m6A reader YTHDF2 bound to PAK5 mRNA and regulated its stability in an m6A-dependent manner. Moreover, ALKBH5 promoted tumorigenesis and metastasis of CC by regulating PAK5. Overall, our findings herein demonstrate a significant role of ALKBH5 in CC progression in HPV-positive cells. Thus, we propose that ALKBH5 may serve as a prognostic biomarker and therapeutic target for CC patients.

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Declaration of Competing Interest All listed authors of this manuscript have approved of the manuscript to submit to Pharmacological Research including its copyright transfer at acceptance for publication. The authors declare that there is no conflict of interest associated with this manuscript.

PubMed

HPV E7 protein helps cervical cancer grow by changing RNA modification of PAK5

Abstract

Full Text

Funding

Competing interests

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